Departament of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal:15053, Porto Alegre, RS 91501-970, Brazil.
J Neural Transm (Vienna). 2010 Feb;117(2):269-76. doi: 10.1007/s00702-009-0362-2. Epub 2010 Jan 5.
Several lines of evidence suggest a relevant role for the dopamine transporter (DAT1) gene not only as a susceptibility factor for attention-deficit hyperactivity disorder (ADHD), but also as a predictor of individual methylphenidate (MPH) response. Pharmacogenetic studies of MPH response in ADHD have mainly focused on the 40-bp variable number of tandem repeats (VNTR) in the 3' untranslated region (3'-UTR) of DAT1. Most studies were performed in samples of children and conflicting findings were obtained. Only two studies have assessed 3'-VNTR in samples of adults-one with positive and the other with negative findings. In the present study, we investigate three potentially relevant polymorphisms in DAT1 gene (-839 C > T; Int8 VNTR and 3'-VNTR), and their possible role in therapeutic response to MPH treatment in a sample of 171 Brazilian adults with ADHD. The diagnostic procedures followed the DSM-IV criteria and the outcome measures were the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. Drug response was assessed by both categorical and dimensional approaches. There was no effect of any DAT1 polymorphisms or haplotypes on MPH response. This is the second report demonstrating absence of differences in MPH response according to DAT1 genotypes in adults with ADHD. Although DAT protein is crucial for the effect of MPH, genetic variations in DAT1 gene probably do not have a significant clinical role in this sample of adults with ADHD.
有几条证据表明，多巴胺转运体（DAT1）基因不仅与注意力缺陷多动障碍（ADHD）的易感性有关，而且与个体对哌甲酯（MPH）的反应有关。ADHD 患者 MPH 反应的遗传药理学研究主要集中在 DAT1 3'非翻译区（3'-UTR）中的 40 个碱基对可变串联重复（VNTR）。大多数研究都是在儿童样本中进行的，得出了相互矛盾的结果。只有两项研究评估了 DAT1 基因中的 3'-VNTR，一项研究结果为阳性，另一项为阴性。在本研究中，我们研究了 DAT1 基因中的三个可能相关的多态性（-839 C > T；Int8 VNTR 和 3'-VNTR），以及它们在 171 名巴西 ADHD 成年患者 MPH 治疗反应中的可能作用。诊断程序遵循 DSM-IV 标准，疗效评估采用 Swanson、Nolan 和 Pelham 评分量表第四版和临床总体印象-严重程度量表，在治疗开始和第 30 天进行评估。药物反应采用分类和维度方法进行评估。DAT1 多态性或单体型对 MPH 反应无影响。这是第二项报告，证明 ADHD 成年患者中 DAT1 基因型与 MPH 反应无差异。尽管 DAT 蛋白对 MPH 的作用至关重要，但 DAT1 基因中的遗传变异在本 ADHD 成年患者样本中可能没有显著的临床作用。
